又一家中國(guó)藥企EUGMP檢查失?。》▏?guó)、意大利紛紛禁令
日期：2016/3/3
公司名稱(chēng)：Dongying TiandongPharmaceutical Co., Ltd. 東營(yíng)天東
檢查日期：2015-12-9
檢查地址：No. 1236, Nan-erRoad, Dongying City, Shandong Provice, China
檢查方：法國(guó)藥監(jiān)
產(chǎn)品：原料藥ENOXAPARIN SODIUM依諾肝素鈉
原料藥HEPARIN SODIUM肝素鈉
Nature of non-compliance : 不符合情況
Overall, 10 deficiencieswere observed during the inspection, 2 Critical and 3 Major deficiencies:
檢查期間總共發(fā)現(xiàn)10個(gè)缺陷，其中2個(gè)關(guān)鍵缺陷，3個(gè)主要缺陷：
[Critical 1] PCR results ofCrude Heparin showing the presence of ruminant DNA received from approvedsuppliers were manipulated. There was no evidence that the samples retestedcame from the same batch tested initially;
【關(guān)鍵缺陷1】肝素粗品PCR結(jié)果顯示從批準(zhǔn)的供應(yīng)商處接收的反芻動(dòng)物類(lèi)DNA是偽造的。沒(méi)有證據(jù)證明復(fù)測(cè)樣品與初測(cè)樣品來(lái)自同一批次；
[Critical 2] The qualitysystem implemented by the company for ensuring the full traceability of crudeHeparin was identified as very weak : e.g., the traceability fromslaughterhouses/abattoirs was not available and not assessed during the auditsof the suppliers (lack of supporting documents for the received lots) ;
【關(guān)鍵缺陷2】公司執(zhí)行的確保肝素粗品可追溯性的質(zhì)量體系很差，例如，從屠宰場(chǎng)開(kāi)始的可追溯性沒(méi)有，對(duì)供應(yīng)商審計(jì)期間并沒(méi)有進(jìn)行評(píng)估（接收批次缺乏支持性文件）；
[Major 1] Misunderstandingof the basic GMP principles for handling of out of specification (OOS) resultsand deviations (e.g., 7 batches of crude Heparin received in 2014 and 2015 wereobtained OOS for potency and used for the manufacturing of finished APIs withoutany OOS investigation);
【主要缺陷1】對(duì)處理OOS結(jié)果和偏差的基本GMP原則有誤解（例如，2014年至2015年接收到的7批肝素粗品效價(jià)結(jié)果為OOS，沒(méi)有進(jìn)行任何OOS調(diào)查即用于原料藥成品的生產(chǎn)）；
[Major 2] The evaluation ofthe new suppliers of crude Heparin was deficient: the procedure was notfollowed, no delivery documents were available, the testing was notsystematically recorded in the equipment logbook, the samples from approvedsuppliers were contaminated during the sampling operation, etc. ;
【主要缺陷2】肝素粗品新供應(yīng)商的評(píng)估有缺陷：未遵守程序，沒(méi)有送貨資料，檢測(cè)儀器日志沒(méi)有系統(tǒng)記錄檢測(cè)，從批準(zhǔn)的供應(yīng)商處送來(lái)的樣品在取樣操作中受到污染等。
[Major 3] The assessment of1 H NMR spectrum (Heparin Sodium) and 13 C NMR (Enoxaparin Sodium) used foridentification test were deficient (e.g., the presence of an additional peak atthe C13 NMR obtained by a subcontracted laboratory was not identified andinvestigated)
【主要缺陷3】用于鑒別測(cè)試的1H NMR圖（肝素鈉）和13C NMR圖（依諾肝素鈉）評(píng)估有缺陷（例如，在合同化驗(yàn)室做的C13 NMR圖中有多余的峰出現(xiàn)，沒(méi)有鑒別沒(méi)有調(diào)查）。
措施：
1. 吊銷(xiāo)現(xiàn)有EU GMP證書(shū)
2. 要求上市許可提交變更
3. 已放行批準(zhǔn)要求召回
4. 禁止銷(xiāo)售
5. 擱置CEP2005-258
Actiontaken/proposed by the NCA :
Withdrawal,of current valid GMP certificate No. GIF-IW-N-4022/68/13
Using QRMprinciples, consideration of withdrawal of current valid EU GMP certificateissued by the Main Pharmaceutical Inspectorate of Poland (GIF-IW-N-4022/68/13).
RequestedVariation of the marketing authorisation(s)
Using QRMprinciples, the removal of the site from MAs should be considered.
Recallof batches already released
Considerationof a recall of product should be given due to the critical findings observed.Using QRM principles, National supply situation and clinical requirementsshould be taken into account when making this decision.
Prohibitionof supply
The sitehas been issued a statement of non compliance and should not be named on anymarketing authorisations whilst this statement remains in place.
Suspensionor voiding of CEP (action to be taken by EDQM)
Suspensionof CEP 2005-258 (Enoxaparin sodium).
以下內(nèi)容為蒲公英提供和翻譯
－－－－－－－－－－－－－
意大利藥監(jiān)同時(shí)禁令：
英文概要 ：
The Health Authorities are advising all Market Authorization Holders that if they have DONGYING TIANDONG PHARMACEUTICAL Co., Ltd. – No. 1236, Nan-er Road, Dongying City, Shandong Provice - CHINA.
as authorized supplier of Enoxaparin and/or Heparin Sodium and/or intermediates in their registration documentation they need to replace the supplier with a new one.
Meaning: the above manufacturer of Enoxaparin and Heparin Sodium and/or intermediates has been found inadequate and is no more acceptable (banned).
The above is applicable for finished products distributed in Italy or exported elsewhere. (Equivalent to the US FDA ban)
中文概要：
意大利藥監(jiān)AIFA建議所有的上市許可持有人，若在其注冊(cè)申報(bào)中將位于中國(guó)山東東營(yíng)南仁路1236號(hào)的東營(yíng)天東制藥有限公司作為供應(yīng)商提供伊諾、肝素及其中間體的話，請(qǐng)即更換相應(yīng)供應(yīng)商。
這意味著這家提供伊諾、肝素及其中間體的企業(yè)被發(fā)現(xiàn)有不符合要求之處且不再被認(rèn)為是可接受的企業(yè)（禁止）。
這個(gè)建議適用于在意大利境內(nèi)銷(xiāo)售或出口到其他地區(qū)的制劑產(chǎn)品（相當(dāng)于美國(guó)FDA的禁止令）。
意大利藥監(jiān)AIFA網(wǎng)站原文：
Verifica Officina Farmaceutica: Dongying Tiandong Pharmaceutical Co. LTD. (China) (12/02/2016)
Avviso alle Aziende Farmaceutiche
Si chiede alle Aziende titolari di AIC di medicinali ad uso umano e/o alle Aziende produttrici di medicinali destinati al mercato comunitario o all'esportazione in Paesi terzi di verificare, con urgenza, se per i medicinali contenenti le seguenti sostanze attive e/o intermedi di produzione ENOXAPARIN SODIUM, HEPARIN SODIUM, autorizzati per il mercato italiano e/o prodotti per l'esportazione, risulti presente come fornitore autorizzato, l’Officina Farmaceutica: DONGYING TIANDONG PHARMACEUTICAL Co., Ltd. – No. 1236, Nan-er Road, Dongying City, Shandong Provice - CHINA.
Solo in caso di riscontro positivo l’Azienda dovrà darne immediata comunicazione, indicare l’eventuale presenza di un sito di produzione alternativo a quello in oggetto e procedere alla richiesta di variazione per l'eliminazione del sito suindicato ovvero indicare l'assenza di sito di produzione alternativo e procedere alla richiesta di variazione per sostituzione del sito cinese in oggetto.
Si precisa, infine, che, nella suddetta comunicazione, la dichiarazione riportata dovrà contenere espressa menzione dell’assenza del produttore in oggetto, non solo tra i fornitori autorizzati di “principio attivo”, ma anche degli “intermedi di produzione”.
Si richiede, da ultimo, per i medicinali autorizzati con procedura di Mutuo Riconoscimento, di specificare il codice di procedura europea.
La comunicazione deve pervenire entro e non oltre il giorno 18 FEBBRAIO 2016, alla seguente casella di posta:
? infocepgmp@aifa.gov.it
信息來(lái)源：蒲公英
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